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Monday, May 20, 2013

Protamine Sulfate for LMWH

There is much discussion lately regarding new reversal
strategies of oral anticoagulants that are rapidly growing in popularity. While the data to support the use of agents
like PCC and aPCCs are limited, our clinical experience is also lacking. So-called ‘old school’ reversal agents,
though infrequently used, still have a place for patients who receive
parenteral anticoagulation.

Protamine sulfate, our favorite salmon sperm derived drug,
was (and still is) our go to reversal drug for heparin products. The clinical experience with protamine for
reversing heparin in cardiac surgery patients is extensive. The effectiveness of protamine for reversing
the effects of low molecular weight heparins is regarded as incomplete. Since the mechanism of protamine relies on
its positive charge and the large molecular weight of unfractionated heparin
and its net negative charge, LMWHs by definition provide a smaller target that
is less strongly attracted to protamine. While it is suggested to utilize
protamine for LMWH reversal, other strategies such as PCC may be a
consideration since the effects of protamine may be short lived due to its 7
minute half-life. [Am. J. Hematol,
2012; 87:S119–S126, CHEST, 2012;141(Supp.2): e24S-e43S]

The dosing of protamine for LMWHs is significantly less
complicated than UFH. Dosing
recommendations are 1 mg of protamine for every 100 anti-Xa units of LMWH
(Enoxaparin 1mg = 100 anti-Xa units) administered over the previous 8 hours
with a maximum protamine dose of 50 mg. If it has been greater than 8 hours
since the last LMWH dose, the dose of protamine decreases to 0.5 mg for every 100
anti-Xa units of LMWH. [CHEST, 2012;141(Supp.2): e24S-e43S]

Dosing of protamine is quite critical since protamine itself
can paradoxically illicit anticoagulant effects through reduction in the rate
of Factor V activation. The problems
with protamine do not stop there. Rapid administration can cause profound
hypotension and bradycardia,pulmonary vasoconstriction, transient neutropenia,
and although highly the highly warned risk to patients who’ve previously
received NPH insulin (the “p” is for protamine, neutral protamine Hagedorn)
developing anaphylactic reactions, the risk is about 1%.

Importantly protamine will not work with fondaparinux or any
other anticoagulant (parenteral or oral) that is not technically a heparin. [Journal of Pharmacy Practice 23(3) 217-225]

About the Founder

My name is Craig Cocchio, and I am an emergency medicine pharmacist and pharmacy clinical faculty. The purpose of this blog is to take a pharmacist's point of view from all things emergency medicine, and to try to define what an emergency medicine pharmacist is (or should be).

Disclaimer

This blog is intended to reflect my personal opinions and beliefs and not those of any other individual, department, institution, University or any other organization. Any opinion given is just that, an opinion, and is not intended to be used as clinical advice for patient care. I reserve the right to edit or remove any post or comment found not to be relevant.